Drugs Used In The Management Of Atrial Fibrillation Dr Steve - - PowerPoint PPT Presentation

Drugs Used In The Management Of Atrial Fibrillation

Dr Steve Murray Consultant EP & Cardiologist

Outline of session

Unfortunately individual cases cannot and will not be discussed! Beta-blockers Calcium channel blockers Flecainide & propafenone Amiodarone Little about Drodenarone

Vaughn-Williams Classification

I - sodium channel blockers II - Beta blockers III – Potassium channel blockade IV – calcium channel blockers Ia – e.g procainamide Ib – e.g. lignocaine Ic – e.g. flecainide III – e.g. Amiodarone, dofetilide NB Sotalol is II and III

Beta blockers

Propranolol Metoprolol Acebutalol Labetalol Atenolol Oxprenolol Sotalol Esmolol Bisoprolol

Beta Blockers – decrease sympathetic tone Action Antagonise the effects of catecholamines (hormones like adrenaline) on the heart.

• They block beta adrenoreceptors, hence

name (duh!)

• Catecholamines, via the so-called

sympathetic nervous system, are like the “accelerator” on heart and blood vessels

Beta-receptors

There are many different types of beta- receptor, but basically some are more prevalent in the heart, and others in the lung However, they are found basically everywhere in the body

Side effects

Slow pulse, too low blood pressure, cold hands/toes, tiredness/lethargy Dose-dependent on which beta blocker used, and varies between individuals

Uses

Good for AF rate control (NICE 1st line) May prevent/reduce attacks of paroxysmal AF in patients with catecholamine- sensitive triggers Some used in heart failure treatment (bisoprolol, carvedilol) – a concept that was heresy only as far back as 1995

Verapamil – Calcium (Ca) Antagonist

Action

Inhibits slow inward Ca current in smooth muscle and cardiac cells, Slows AV node conduction [main ‘junction box’ in the heart... ... Hence slows ventricular response to atrial fibrillation/flutter May suppress Sinus node function [natural pacemaker]

Other points to consider

Has negative inotropic effect – i.e. decreases force of contraction in the heart Caution... ...if patient has received beta blocker! Also care required in patients with poor myocardial function- hypotension or VT

Uses

Good for prevention of SVT, but does not prevent AF. Excellent rate control for AF in those unable to take Beta-blockers Good drug to combine with Digoxin, but not beta-blockers

Verapamil – Bluffer’s guide

Like all Calcium channel blockers, Verapamil is in Vaughn-Williams Class IV It primarily acts on AV node and His- purkinje system

Other calcium channel blockers

Diltiazem – very similar to verapamil Amlodipine – little effect on heart conduction, better on relaxing arteries, hence excellent for Blood pressure treatment, and useless for rate control

Vaughn-Williams Classification

I - sodium channel blockers II - Beta blockers III – Potassium channel blockade IV – calcium channel blockers Ia – e.g procainamide Ib – e.g. lignocaine Ic – e.g. flecainide III – e.g. Amiodarone, dofetilide NB Sotalol is II and III

Cardiac Action Potential – a bit like a toilet flush!

Chain pulled, loo flushes Cistern just about refilled You might manage a new flush anywhere about here

Flecainide- Class 1c Antiarrhythmic

Action Binds to sodium channel, decreases speed of depolarisation (phase 1 of action potential) Slows conduction in the atria, His-purkinje fibres, accessory pathways and ventricles Causes slight prolongation of QRS complex, but not QT interval

Effect of Flecainide

Flecainide

Effective and safe in treatment of atrial fibrillation with structurally normal hearts However effects often wane after 2 or 3 years for some patients...

Flecainide – bluffer’s guide

F1ecainide – class Ic For ‘Action’ think:

for AF, it’s like tadpoles (AF wavelets) swimming in water (spreading across the atria); flecainide turns the pond water into syrup!

Caution!

Due to negative inotropic effect should be avoided in patients with heart failure (but see below anyway) Can be pro arrhythmic – especially in LV dysfunction and acute ischaemia Can paradoxically worsen atrial arrhythmias – slowing of atrial rate may facilitate 1:1 conduction of flutter

Side effects Visual disturbance Light headedness nausea Can increase pacing threshold in those with pacemakers implanted

Amiodarone- Class III Antiarrhythmic

Action “Broad spectrum” antiarrhythmic highly effective in treatment of supraventricular and ventricular rhythm disorders Utterly over-used, especially by non- cardiologists! Prolongs refractoriness (makes cells lazier)

Effect of Amiodarone

Amiodarone – Bluffer’s guide

Class III drug Think: after flushing your toilet, it takes longer to re-fill the cistern, so you cannot flush it again quite so quickly Most amiodarone in the body just ‘hangs around’ in muscles doing nothing... ...active drug in blood is a small fraction

Caution! Sinus bradycardia Thyroid dysfunction Iodine sensitivity Pregnancy

Side Effects

Reversible corneal deposits (disappear if drug stopped) Skin photosensitivity/slate grey skin discoloration Hypo/hyperthyroidism Lung fibrosis Bradycardia and conduction disturbances Can effect liver function Can effect renal function/thrombocytopenia Nausea, rash, alopecia, tremor, insomnia, nightmares

Other points to consider

Can potentiate warfarin Can increase blood levels of digoxin, quinidine and flecainide Liver function, thyroid function test required before treatment and every 6 months Chest X ray performed prior to commencing drug

Half Life 2 weeks to 3 months Dosage (oral) Loading dose often required Action may take 1-3 weeks to occur even after loading doses

Drodenarone

Amiodarone without the side effects! May become ‘gold standard’ in AF, but... ...possibly less good in AF with heart failure.

Digoxin

Enhances vagal tone [the “brakes” on the heart via the so-called parasymptathetic nervous system] Vagal tone is withdrawn first at the onset

• f exercise...

...hence Digoxin is not a great 1st line treatment in active patients

Digoxin

Most of the drug ‘hangs around in muscles” doing nothing, with small fraction in blood that is active Hence interacts with amiodarone Too much is poisonous! Works extremely well in combination with verapamil

Digoxin is weakly positively inotropic...

In other words it has a weak tonic effect on the heart... ...this is in contrast to every other anti- arrhythmic drug

Warfarin

Block Vitamin K in the gut, which is required to make clotting factors INR is a ratio as to how much longer the blood will take to clot as compared to ‘normal’ (an average) Works in the liver, where clotting factors are made... ...hence influenced by other drugs and foods!

Aspirin

Makes platelets less sticky Has no effect on clotting factors

Summary

All anti-arrhythmic drugs act by altering conduction in the heart. The receptors and nerves influenced by these drugs are often found in other tissues outside the heart...hence side effects

Summary

Some important drugs ‘fill up seats’ in muscles or fat tissue doing nothing, and it’s only when all the ‘seats are taken’ that the drug spills out into blood where it is active. Some drugs ‘compete for these seats’ and thus can influence active levels of each

• ther

Thank you

Adenosine

Action

Blocks AV node conduction Shortens atrial refractoriness – “recover quicker/less lazy” (hence may promote AF) May have some effect on SA node

Adenosine - Uses

Clinically:

Terminate SVTs via nodal block Differentiate VT (NB at high enough dose) Unmask a latent accessory pathway

In EP lab:

May aid in assessing a septal concealed accessory pathway

Adenosine – miscellanea

May terminate around:

15% of automatic atrial tachycardias 10-15% of fascicular VT 10-15% RVOT VT 5-10% typical atrial flutter

Beware the ‘rebound sympathetic drive’ and resultant sinus tachycardia!

Caution!

May cause sinus bradycardia, which may be more prolonged in patients with sick sinus syndrome In patients with asthma may cause bronchospasm (but this is rare, and often over- played) It should only be given with crash trolley to hand

• and with this caveat, it is safe to give to pre-

excited AF in my opinion

Half Life - 20-30seconds Side Effects Chest tightness Dyspnoea Flushing Patient may experience impending sense

• f doom

Administration-Rapid bolus, with defib on hand

Adenosine doses

Manufacturer’s recommended Dose:- Rapid 3mg bolus, if no reversion to sinus rhythm after 1 min give 6mg, then 12mg, then 18mg this is the maximum dose Real life: Start at least at 6mg, and ‘personal best’ is 36mg

Atropine

Action Blocks vagal stimulation – hence may alleviate vagally-mediated bradycardia & vaso-vagal symptoms in lab NB it will not reverse heart block due to conduction tissue disease, or damage from RF!

When would we use it in the lab?

If patient has vagal event i.e during vascular access / following sheath removal May aid initiation of SVT (“slick-up” the AV node)

Side Effects

Urinary retention Dry mouth Dilated pupils Visual disturbances Confusion Dose 500/600mcg rapid bolus; at 3mg vagus is maximally blocked